A search for genetic markers is a powerful strategy in psychiatric genetics. Evidence for the transmission of bipolar and related disorders by a specificable segment of the X-chromosome would offer conclusive proof of a genetic substrate for this disorder and would lead to improved risk prediction for individuals for informative pedigrees. Since reliable genetic markers are virtually nonexistent in psychiatric research, the preliminary indication that X-chromosome markers may prove to be genetic markers in a subset of affective pedigrees is of major importance. Previous linkage data in bipolar affective illness are beset by conflicting results. The possibility of methodological pitfalls affecting some of the series reported has been raised. The aim of the proposed research is to study linkage of bipolar-related affective disorders to X-chromosome markers (protan and deutan colorblindness and glucose-6-phosphate dehydroenase (G6PD) deficiency) in a new series of pedigrees. Rigorous diagnostic and analytic methods will be used, including pedigree analysis techniques that incorporate variable age-of-onset and penetrance and account for genetic linkage heterogeneity. The population to be studied is well-defined and is larger than most previously reproted series. In addition, the high prevalence of G6PD deficiency in this population provides a unique opportunity for studying linkage between the illness and this marker. The particular features of the proposed investigation would advance our knowledge of the possible role of X-chromosome markers in the genetics of bipolar affective illness and would help resolve some aspects of this intriguing research issue.